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Endocrine system
Fatima Obeidat, MD
I. Thyroid diseases
I. THYROTOXICOSIS
- A hypermetabolic state caused by increase T3 and T4 and
most commonly, caused by hyperfunction of the
thyroid gland ( called hyperthyroidism)
Causes of thyrotoxixosis are:
A. Associated with hyperthyroidism (Thyroid
hyperfunction):
1. Primary
a. Diffuse toxic hyperplasia (Graves disease)
b. Hyperfunctioning (Toxic) multinodular goiter)
c. Hyperfunctioning (toxic ) adenoma
2. Secondary -- TSH-secreting pituitary adenoma (rare)
B. Not associated with hyperthyroidism
- Excessive release of pre-formed hormone due to
destruction of follicles such as in thyroiditis
Clinical manifestations of thyrotoxicosis
a. Constitutional symptoms : warm flushed skin, heat
intolerance and excessive sweating
- Weight loss despite increased appetite.
b. Malabsorption, and diarrhea.
c. Tachycardia and elderly patients may develop heart
failure due to aggravation of pre-existing heart
disease
d. Nervousness, tremor, and irritability
e. A wide, staring gaze and lid lag because of sympathetic
overstimulation of the levator palpebrae superioris
muscle
Note: True thyroid ophthalmopathy associated with proptosis
is a feature seen only in Graves disease.
f. 50% develop proximal muscle weakness (thyroid
myopathy).
g Thyroid storm : Designates the abrupt onset of severe
hyperthyroidism, and this condition occurs most
commonly in individuals with Graves disease and it is a
medical emergency because significant numbers of
untreated patients die of cardiac arrhythmias
h- Apathetic hyperthyroidism : thyrotoxicosis occurring in
elderly persons, in whom the typical features of thyroid
hormone excess seen in younger patients are blunted and
in these patients the diagnosis is often made during laboratory workup for unexplained weight loss or
worsening cardiovascular disease.
Note:
- The measurement of serum TSH is the most useful single
screening test for hyperthyroidism, because TSH levels
are decreased even at the earliest stages, when the
disease may still be subclinical
- Once the diagnosis of thyrotoxicosis has been
confirmed measurement of radioactive iodine
uptake by the thyroid gland often is valuable in
determining the etiology
For example, such scans may show :
a. Diffusely increased (whole-gland) uptake in Graves
disease,
b. Increased uptake in a solitary nodule in toxic
adenoma
c. Or decreased uptake in thyroiditis.
II. HYPOTHYROIDISM :
Primary causes
a. - Worldwide, the most common cause of hypothyroidism
is dietary deficiency of iodine.
b. In most developed countries, autoimmune diseases
predominate such as Hashimoto thyroiditis
c. Genetic defects such as
1. Thyroid dysgenesis or
2. Congenital biosynthetic defect (dyshormogentic goiter).
II. Secondary causes: Pituitary or hypothalamic disorder
A. Cretinism :
- Refers to hypothyroidism developing in infancy or early
childhood
1. Endemic cretinism: This disorder formerly was common
in areas of the world where dietary iodine deficiency is
endemic, including mountainous areas ( the Himalayas )
- It is now much less frequent because of the widespread
supplementation of foods with iodine
2. Sporadic cretinism. Caused by enzyme defects that
interfere with thyroid hormone synthesis
Clinical features of cretinism include:
- Impaired development of skeletal system- short stature,
- Coarse facial features, protruding tongue, umbilical
hernia.
- Central nervous system- with mental retardation
Note- The severity of the mental impairment seems to be ,
directly influenced by the timing of onset of the deficient
state in utero.
- Normally, maternal hormones that are critical to fetal
brain development, including T3 and T4, cross the
placenta
1. Severe mental retardation if maternal thyroid deficiency is
present before the development of the fetal thyroid
2. Reduction in maternal thyroid hormones later in
pregnancy, after the fetal thyroid has developed
allows normal brain development.
2. Myxedema. or Gull syndrome :
- Hypothyroidism in older children and adults and
characterized by:
a. Patients are listless, cold intolerant, and often obese.
b. Generalized apathy and mental sluggishness that in the
early stages of disease may mimic depression
c. Broadening and coarsening of facial features
d. Enlargement of the tongue, and deepening of the voice.
e. Bowel motility is decreased, resulting in constipation..
g. Mucopolysaccharide-rich edematous fluid accumulates in
skin, subcutaneous tissue, and number of visceral sites
Laboratory evaluation :.
a - Serum TSH is the most sensitive screening test .
- The serum TSH is increased in primary hypothyroidism
b. Serum T4 is decreased hypothyroidism of any origin.
III. Thyroiditis
1. Chronic Lymphocytic (Hashimoto) Thyroiditis
- Is the most common cause of hypothyroidism in areas of
the world where iodine levels are sufficient.
- It is characterized by gradual thyroid failure secondary to
autoimmune destruction of the thyroid gland
- It is most prevalent between the ages of 45 and 65 years
and is more common in women than in men
- It can occur in children and is a major cause of nonendemic goiter in children
PATHOGENESIS :Caused by breakdown in self-tolerance to thyroid antigens
- Circulating autoantibodies against thyroid antigens arepresent in the vast majority of patients
- Multiple immunologic mechanisms may contribute to
thyrocyte damage ,
I. Cytokine-mediated cell death: Excessive T cell activation
leads to the production of inflammatory cytokines such as
IFN-γ in the thyroid with resultant recruitment and
activation of macrophages and damage to follicles
.
2. Binding of anti-thyroid antibodies (antithyroglobulin, and
antithyroid peroxidase antibodies), followed by antibodydependent cell-mediated cytotoxicity
- A significant genetic component is supported by the
a. Concordance of disease in 40% of monozygotic twins,
b. And the presence of circulating antithyroid antibodies in
50% of asymptomatic siblings of affected patients .
• Gross :
- Diffuse and symmetric enlargement of the thyroid but
localized enlargement may be seen in some cases to
raise suspicion for neoplasm
Microscopic examination reveals
1. Infiltration by small lymphocytes, plasma cells, and welldeveloped germinal centers
2. The thyroid follicles are atrophic
2. Some follicles are lined by epithelial cells with abundant
eosinophilic, cytoplasm, termed Hürthle cells and these
Hurthle cells have numerous mitochondria
- Less commonly, the thyroid is small due to extensive
fibrosis (fibrosing variant) but unlike Reidel thyroiditis, the
fibrosis does not extend beyond the capsule of the gland.
Clinically ,
1. Painless thyroid enlargement associated with some
degree of hypothyroidism,
2. - In the usual clinical course, hypothyroidism develops
gradually.; however, it may be preceded by transient
thyrotoxicosis due to disruption of thyroid follicles ,and
secondary release of thyroid hormones .
Hashimoto thyroiditis
- Patients with Hashimoto thyroiditis often :
1. Have other autoimmune diseases
2. .Are at increased risk for the development of B cell
non-Hodgkin lymphomas within the thyroid gland.
Note:
- The relationship between Hashimoto disease and
thyroid epithelial cancers remains controversial,
with some morphologic and molecular studies
suggesting a predisposition to papillary
carcinomas
2. Subacute Granulomatous (de Quervain) Thyroiditis
- Is much less common than Hashimoto disease
- Is most common between the ages of 30 and 50 and,
- More frequently in women than in men.
- Is believed to be caused by a viral infection and a majority
of patients have a history of an upper respiratory infection
just before the onset of thyroiditis.
Gross- The gland has intact capsule, and may be
unilaterally or bilaterally enlarged.
Histologic examination reveals
1. Disruption of thyroid follicles, with extravasation of colloid
leading to a neutrophilic infiltrate, which is replaced by
lymphocytes, plasma cells, and macrophages.
2. The extravasated colloid provokes a granulomatous
reaction with giant cells that contain fragments of colloid.
3. Healing occurs by resolution of inflammation and fibrosis.
Clinical Features :
-Acute onset characterized by neck pain ( with swallowing)
- Fever, malaise, and variable enlargement of the thyroid.
- Transient hyperthyroidism may occur as a result of
disruption of follicles and release of excessive hormones.
- The leukocyte count is increased.
- With progression of disease and gland destruction, a
transient hypothyroid phase may ensue.
- The condition typically is self-limited, with most patients
returning to a euthyroid state within 6 to 8 weeks
3..Subacute Lymphocytic Thyroiditis :
- Also is known as silent or painless thyroiditis;
- And in a subset of patients the onset of disease follows
pregnancy (postpartum thyroiditis).
- Most likely to be autoimmune because circulating
antithyroid antibodies are found in a majority of patients
- It mostly affects middle-aged women, who present with apainless neck mass or features of thyrotoxicosis
- The initial phase of thyrotoxicosis (which is likely to be
secondary to thyroid tissue damage) is followed by return
To euthyroid state within a few months.
- In a minority of affected persons the condition eventually
progresses to hypothyroidism.
- The histologic features consist of lymphocytic infiltration
4/ Riedel thyroiditis,:
- A rare disorder of unknown etiology,
- Characterized by extensive fibrosis involving the thyroid
and contiguous structures simulating a thyroid neoplasm
- May be associated with idiopathic fibrosis in other parts of
the body, such as the retroperitoneum
- The presence of circulating antithyroid antibodies in most
patients suggests an autoimmune etiology